Lung Cancer Remains a Treatment Challenge, Despite Advanced Medical Intervention

Lung cancer kills almost 1.5 to 2 million people per year globally and it is estimated to increase further in the coming decade. Lung cancer is the most common cause of cancer related death in men and the second most common in women after breast cancer.

What causes lung cancer?

The single most important risk factor for lung cancer is smoking. About 80% of lung cancers occur as a result of the exposure to smoke both mainstream and second hand smoke. Initiation of smoking in childhood or adolescence is an independent risk factor to lung cancer due to long duration of smoking and the life time exposure to cigarette related carcinogens.

Young smokers tend to smoke more cigarettes in a day, inhale deep and are less likely to quit as compared to people who start smoking late. Moreover, adolescent smoking initiates a process called field cancerisation ie. abnormal clonal proliferation in the respiratory epithelium that can lead to lethal cancers over time. Hence prevention of smoking among adolescents is critical in controlling the tobacco epidemic and henceforth the incidence of lung cancer.

While smoking is an undisputed cause of lung cancer, 10 – 20% of lung cancers occur in non-smokers, that is those who have smoked less than 100 cigarettes in their life time. This points towards alternate risk factors of lung cancer other than smoking. The most important risk factors other than smoking in females is exposure to environment tobacco smoke, and in males, it is occupational exposure to carcinogens.

Non-smokers who reside with smokers have a 24% increased risk of lung cancer as compared to other non-smokers. Hormone replacement therapy in post-menopausal females, exposure to radon, asbestos, nickel, chromium, soot, tar, house fold fumes, air pollution also contributes to lung cancer.

Even then in few patients lung cancer can occur without any of these risk factors. Hereditary factors and individual gene susceptibility are likely to play a role in causation of lung cancer in them.

Why is lung cancer so common today?

Incidence and mortality of lung cancer varies widely worldwide and is closely linked to the smoking pattern. Over the past 3 to 4 decades, industrialised nations have shown a sharp decline in smoking and consequently of lung cancer. However, developing countries like India have shown increased rates of smoking and hence the incidence of lung cancer.

As compared to the developed nations we face certain unique challenges like increasing use of cigarette and bidis, indoor air pollution from domestic and biomass fuel, occupational exposure, possible contribution of mycobacterium tuberculosis that cause tuberculosis of lung. To add on we need to overcome the sociocultural obstacles in implementing tobacco cessation programs among our people. Though the incidence of lung cancer in emerging nations is less as compared to developed countries the mortality is much higher. This is attributable to the delay in diagnosis and treatment due to poor health access, sociocultural barriers and environmental contamination.

One alarming observation is the rising incidence of lung cancer in female population which in fact has more than doubled. The exact reason for this is not well understood, several factors like genetic variants, environmental factors, oncogenic viruses, hormonal factors have all been attributed.

Lung Cancer Remains a Treatment Challenge, Despite Advanced Medical Intervention


The overall 5 year survival rate for lung cancer is 18%. This means that after adjusting for other causes of death, out of 100 people diagnosed with lung cancer 18 will be alive at 5 years since diagnosis. The survival is better if diagnosed at an early stage before cancer spreads to other parts of the body.


Screening helps in detecting a disease in its early stage even before it becomes symptomatic. The only recommendation for lung cancer as per the US preventive service task force guidelines is for heavy smokers and those who have quit smoking and are between 55 to 80 years of age. The recommended test is low dose CT scan of the chest.

As mentioned earlier, the incidence of lung cancer in non-smokers and female are on the rise. But unfortunately, screening of lung cancer has not yet been successful in them. Probably that is one of the many reasons why they present usually in advanced stages. Prevention

Most important way to prevent lung cancer is to never start smoking and if you are already a smoker to quit smoking. Its never late to quit. No matter how long or how much you smoked so far, quitting always benefits to reduce though not completely eliminate the cancer risk.


Lung cancer in its early stage is not always symptomatic. Any symptoms like persistent cough, blood stained sputum, chest pain, breathlessness, hoarseness, loss of appetite, loss of weight need to be addressed without any delay. Most often lung cancer is diagnosed while evaluating for these symptoms and sometimes incidentally.  


Lung cancer is usually suspected when there are nodules or haziness in chest X-rays. These abnormalities are better characterised by CT or PET imaging. PET CT also determine the extent of tumor spread and helps in staging. Equally important is to sample tissue from the nodule by a procedure called biopsy. There are many methods to biopsy the tissue and the most accessible part of the nodule will be sampled. The different types of biopsies include Transthoraccic biopsy, Endoscopic ultrasound guided biopsy, Video-assisted thoracoscopic surgery, mediastinoscopic biopsy and open biopsy.

Histologically lung cancer is broadly divided into two types – Non Small cell lung cancer (NSCLS) and Small cell lung cancer (SCLC). NSCLC is further divided into Adenocarcinoma, Squamous cell carcinoma and Large cell carcinoma.


Until recently the conventional treatment of lung cancer included surgery, radiation and chemotherapy. The best treatment is tailored based upon the stage of cancer, histologic type, the overall health of the patient and lung function.

Early lung cancer can be better treated by surgery to remove the tumor. Surgery for lung cancer is a complex procedure and can have serious consequences. Hence, the patients for surgery are carefully selected depending on the size of tumor and extent of spread.

Radiation to lung tumor with or without concurrent chemotherapy is offered to patients with inoperable tumors. With advent of newer techniques to deliver radiotherapy like SBRT, IMRT, 3D CRT, Brachytherapy the scattering of radiation to adjacent healthy tissue can be minimised.

Chemotherapy in lung cancer is indicated in various situations like neoadjuvant (given before surgery), along with radiation, Adjuvant (after surgery) and also in palliative setting in patients with advanced lung cancer. 

How is the treatment of lung cancer changing?

The two new modalities of treatment that are upcoming and found promising in lung cancer are Targeted therapy and Immunotherapy. The availability of these drugs has greatly changed the treatment of lung cancer patients.

Targeted drugs work differently from chemotherapy and specifically target certain driver mutations. These actionable molecular drivers of lung cancer include EGFR, ALK and ROS and these occur almost exclusively in NSCLC in never smokers. One of the common group of these drugs target EGFR gene that normally help cells divide and grow.

Some lung cancer over express EGFR and the targeted agents that can block the signal from EGFR can inhibit the tumor growth. Around 5% of lung cancers can have ALK gene rearrangement and drugs that targe abnormal ALK protein can control tumor growth. Similarly other rare mutations seen in 1% to 2% of lung cancer or even lesser like BRAF, NTRK, RET, MET are being identified and specific drugs to disable the proteins from the abnormal genes can arrest tumor growth. Inhibition of these driver mutations in advanced lung cancers is more effective and less toxic than conventional chemotherapy.

Immunotherapy helps a person’s own immune system to recognise and destroy cancer cells. Immunotherapy has paved way in the management of advanced lung cancer both in first line and subsequent lines of therapy. However not all lung cancers benefit from immunotherapy. Studies to identify biomarkers that can predict the best responders to immunotherapy are ongoing. Researchers are also combining immunotherapy with chemotherapy, surgery and radiation for optimal response.

Lung Cancer Remains a Treatment Challenge, Despite Advanced Medical Intervention


The most important risk factor for lung cancer is smoking. Hence, the most important way not to get lung cancer is not to smoke. But people who do not smoke can also develop lung cancer. The harsh truth is that lung cancer causes symptoms only when it is quite advanced. Hence very few lung cancers are diagnosed in early stage. The good news is that there is tremendous advances happening in the management of lung cancer that is quite promising.  But despite all these advances, lung cancer still remains a treatment challenge, especially if advanced.

Dr Rajitha L, the author of this article, is a Consultant Medical Oncologist, at the KIMSHealth Cancer Centre

By Manoj

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